Wei Jiang1, Zhenxia Wu2, Li Wen2, Liu Sun2, Meiqun Zhou2, Xiaochen Jiang2, Yaxing Gui3. 1. Department of Rheumatology and Geriatrics, The First Hospital of Fuyang Hangzhou, No. 429, Beihuan Road, Hangzhou, 311400, Zhejiang, China. baihejiangwei127@163.com. 2. Department of Rheumatology and Geriatrics, The First Hospital of Fuyang Hangzhou, No. 429, Beihuan Road, Hangzhou, 311400, Zhejiang, China. 3. Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 86 Wujin Road, Shanghai, 200080, China. YaxingGui@shsmu.edu.cn.
Abstract
INTRODUCTION: Alzheimer's disease (AD) is usually accompanied by different degrees of behavioral and psychological symptoms of dementia (BPSD). Transcranial magnetic stimulation (TMS) has been applied for the treatment of AD as a painless and noninvasive therapy. However, the efficacy of repetitive TMS (rTMS) with different frequencies in AD with BPSD remains unknown. METHODS: A total of 32 AD patients with psychobehavioral symptoms were selected as the study subjects. Among them, 16 patients were included in the high-frequency TMS group with an average disease duration of 6.22 ± 2.55 years. The low-frequency TMS group was gender and age matched with a disease course of 7.02 ± 3.33-year average duration. The high-frequency TMS group received TMS treatment twice per day for 4 weeks under 80% MT stimulation intensity, 10-Hz frequency for 0.5 h each time, and the low-frequency TMS group received TMS treatment of 2-Hz frequency for 0.5 h each time. Neuropsychological status was assessed by the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score. The behavioral ability was assessed by the Abilities of Daily Living (ADL) scale; cognitive function was evaluated by Mini-Mental State Examination (MMSE). The levels of β amyloid 40 and 42 (Aβ40 and Aβ42) in plasma were detected using a double-antibody sandwich enzyme-linked immunosorbent assay. All patients underwent brain magnetic resonance imaging (MRI) before and after the experiment. RESULTS: After 2 weeks of treatment, the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those before the treatment, and they continued to decrease after 4 weeks of treatment. The BEHAVE-AD and ADL scores of the low-frequency TMS group were also significantly lower than before treatment. The comparison between groups at different time points showed that the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those of the patients in the low-frequency TMS group. The MMSE of high-frequency TMS-treated patients increased from 14.22 ± 3.55 before treatment to 14.67 ± 2.22 at 2 week's treatment and 17.33 ± 3.11 at 4 week's treatment (p < 0.01) in contrast to 14.19 ± 3.47, 14.28 ± 3.41, and 14.49 ± 2.79, respectively, found in the low-frequency TMS group. At week 4, the high-frequency TMS-treated group's plasma Aβ40 did not change compared to that before treatment. No effects on plasma Aβ42 were observed between the high- vs. low-frequency TMS groups. The incidence of adverse reactions during treatment was comparable between groups. CONCLUSION: These results indicate that high-frequency TMS has the advantages of fast results, good efficacy, and high safety for the treatment of psychobehavioral abnormalities in AD patients. In addition, our study suggests that high-frequency TMS intervention can further improve the cognitive function of AD patients.
INTRODUCTION: Alzheimer's disease (AD) is usually accompanied by different degrees of behavioral and psychological symptoms of dementia (BPSD). Transcranial magnetic stimulation (TMS) has been applied for the treatment of AD as a painless and noninvasive therapy. However, the efficacy of repetitive TMS (rTMS) with different frequencies in AD with BPSD remains unknown. METHODS: A total of 32 AD patients with psychobehavioral symptoms were selected as the study subjects. Among them, 16 patients were included in the high-frequency TMS group with an average disease duration of 6.22 ± 2.55 years. The low-frequency TMS group was gender and age matched with a disease course of 7.02 ± 3.33-year average duration. The high-frequency TMS group received TMS treatment twice per day for 4 weeks under 80% MT stimulation intensity, 10-Hz frequency for 0.5 h each time, and the low-frequency TMS group received TMS treatment of 2-Hz frequency for 0.5 h each time. Neuropsychological status was assessed by the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score. The behavioral ability was assessed by the Abilities of Daily Living (ADL) scale; cognitive function was evaluated by Mini-Mental State Examination (MMSE). The levels of β amyloid 40 and 42 (Aβ40 and Aβ42) in plasma were detected using a double-antibody sandwich enzyme-linked immunosorbent assay. All patients underwent brain magnetic resonance imaging (MRI) before and after the experiment. RESULTS: After 2 weeks of treatment, the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those before the treatment, and they continued to decrease after 4 weeks of treatment. The BEHAVE-AD and ADL scores of the low-frequency TMS group were also significantly lower than before treatment. The comparison between groups at different time points showed that the BEHAVE-AD and ADL scores of the patients in the high-frequency group were significantly lower than those of the patients in the low-frequency TMS group. The MMSE of high-frequency TMS-treated patients increased from 14.22 ± 3.55 before treatment to 14.67 ± 2.22 at 2 week's treatment and 17.33 ± 3.11 at 4 week's treatment (p < 0.01) in contrast to 14.19 ± 3.47, 14.28 ± 3.41, and 14.49 ± 2.79, respectively, found in the low-frequency TMS group. At week 4, the high-frequency TMS-treated group's plasma Aβ40 did not change compared to that before treatment. No effects on plasma Aβ42 were observed between the high- vs. low-frequency TMS groups. The incidence of adverse reactions during treatment was comparable between groups. CONCLUSION: These results indicate that high-frequency TMS has the advantages of fast results, good efficacy, and high safety for the treatment of psychobehavioral abnormalities in AD patients. In addition, our study suggests that high-frequency TMS intervention can further improve the cognitive function of AD patients.